173676-59-0

Basic information

• Product Name: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride
• Synonyms: 4-CHLORO-2(1,1-DIHYDROXY-2,2,2-TRIFLUOROETHYL)ANILINE HCL;4-CHLORO-2,2,2-TRIFLUORO ACETYL ANILINE HYDROCHLORIDE;1-(2-aMino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride;Ethanone,1-(2-aMino-5-chlorophenyl)-2,2,2-trifluoro-, hydrochloride (1:1);Efavirenz Intermediate E-2;E2，173676-59-0;1-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethan-1-one hydrate hydrochloride;Efavirenz Intermediate: Trifluoroethanone
• CAS NO: 173676-59-0
• Molecular Formula: C₈H₅ClF₃NO*ClH
• Molecular Weight: 278.06
• EINECS: 1592732-453-0
• Product Categories: Amines and Anilines;Carbonyl Compounds;Aromatics Compounds;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 173676-59-0.mol
• Article Data: 3

Chemical Properties

• Melting Point: 156-158°C
• Boiling Point: 282.3 °C at 760 mmHg
• Flash Point: 124.5 °C
• Appearance: /
• Vapor Pressure: 0.00339mmHg at 25°C
• Storage Temp.: Inert atmosphere,Room Temperature
• CAS DataBase Reference: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride(173676-59-0)
• EPA Substance Registry System: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride(173676-59-0)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 173676-59-0(Hazardous Substances Data)

Usage

Chemical Properties

Pale Yellow Solid

Uses

HIV reverse transcriptase inhibitor.

InChI:InChI=1/C8H5ClF3NO.ClH/c9-4-1-2-6(13)5(3-4)7(14)8(10,11)12;/h1-3H,13H2;1H

Synthetic route

ethyl trifluoroacetate, (383-63-1) + N-(2-bromo-4-chlorophenyl)pivalamide (195372-65-7) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Stage #1: N-(2-bromo-4-chlorophenyl)pivalamide With iodine; magnesium; lithium chloride In tetrahydrofuran at 20℃; for 6h; Stage #2: ethyl trifluoroacetate, In tetrahydrofuran at -15 - 20℃; for 0.5h; Stage #3: With hydrogenchloride; acetic acid at 75℃; for 4h; Reagent/catalyst; Temperature;	70%

N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)pivalamide (181190-33-0) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
With hydrogenchloride In dimethoxyethane (DME) Heating / reflux;

4-chloro-aniline (106-47-8) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide; water / toluene / 1 h / 15 - 40 °C 2.1: bromine; acetic acid / 1 h / 20 °C 3.1: magnesium; iodine; lithium chloride / tetrahydrofuran / 6 h / 20 °C 3.2: 0.5 h / -15 - 20 °C 3.3: 4 h / 75 °C View Scheme

1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Stage #1: 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone With 5%-palladium/activated carbon; hydrogen In ethyl acetate at 20 - 60℃; under 750.075 - 10501.1 Torr; Stage #2: With hydrogenchloride for 30h;	121 g

1-bromo-3-chlorobenzene (108-37-2) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / -78 - -50 °C 1.2: -78 - 20 °C 2.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 3.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 3.2: 30 h View Scheme

1-(3-chlorophenyl)-2,2,2-trifluoroethanone (321-31-3) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 2.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 2.2: 30 h View Scheme

3-iodochlorobenzene (625-99-0) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: isopropylmagnesium chloride / tert-butyl methyl ether / 1 h / -20 - -10 °C 1.2: -20 - 20 °C 2.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 3.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 3.2: 30 h View Scheme

1,3-Dichlorobenzene (541-73-1) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: magnesium; ethylene dibromide / tetrahydrofuran / 2 h / 40 - 50 °C 1.2: 0.5 h / 10 - 30 °C 2.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 3.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 3.2: 30 h View Scheme

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone (154598-53-5)

Conditions	Yield
With sodium hydrogencarbonate In water at 20℃; for 0.05h; Inert atmosphere; Schlenk technique;	99%
With sodium carbonate In dimethoxyethane (DME) pH=9;
With sodium hydrogencarbonate In water; toluene at 20℃; pH=7 - 8;

3-methoxybenzothiophene (10419-32-6) + 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 2-chloro-11-trifluoromethyl[1]benzothieno[3,2-b]quinoline

Conditions	Yield
With indium(III) bromide In chlorobenzene at 110℃; under 760.051 Torr; for 24h; Inert atmosphere; Schlenk technique;	97%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + Cyclopropylacetylene (6746-94-7) → 2-cyclopropyl-4-(trifluoromethyl)-6-chloroquinoline

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Sealed tube;	85%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + hex-1-yne (693-02-7) → C14H13ClF3N (1456900-23-4)

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Sealed tube;	83%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + 4-n-methylphenylacetylene (766-97-2) → 6-chloro-2-(4-methylphenyl)-4-(trifluoromethyl)quinoline (1456900-24-5)

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Sealed tube;	80%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + phenylacetylene (536-74-3) → 2-phenyl-4-(trifluoromethyl)-6-chloroquinoline

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Reagent/catalyst; Sealed tube;	73%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 2-chloro-11-trifluoromethyl-10H-quindoline

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water / 0.05 h / 20 °C / Inert atmosphere; Schlenk technique 2: indium(III) bromide / 1,2-dichloro-benzene / 36 h / 170 °C / 760.05 Torr / Inert atmosphere; Schlenk technique View Scheme

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 2-chloro-11-trifluoromethyl-5-methyl-10H-quindolinium 1,1,1-trifluoromethanesulfonate

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / water / 0.05 h / 20 °C / Inert atmosphere; Schlenk technique 2: indium(III) bromide / 1,2-dichloro-benzene / 36 h / 170 °C / 760.05 Torr / Inert atmosphere; Schlenk technique 3: toluene / 24 h / 50 °C / Inert atmosphere; Schlenk technique View Scheme

Upstream product

• 541-73-1 1,3-Dichlorobenzene 
• 625-99-0 3-iodochlorobenzene 
• 321-31-3 1-(3-chlorophenyl)-2,2,2-trifluoroethanone 
• 108-37-2 1-bromo-3-chlorobenzene 
• 106-47-8 4-chloro-aniline 
• 383-63-1 ethyl trifluoroacetate, 
• 195372-65-7 N-(2-bromo-4-chlorophenyl)pivalamide 
• 181190-33-0 N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)pivalamide 

Downstream Products

• 1456900-24-5 6-chloro-2-(4-methylphenyl)-4-(trifluoromethyl)quinoline 
• 391860-73-4 6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 154598-53-5 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone 

Relevant articles and documents

Method for preparing 4-chloro-2-(trifluoroacetyl)aniline hydrochloride hydrate and free alkalis thereof

The invention discloses a method for preparing a 4-chloro-2-(trifluoroacetyl)aniline hydrochloride hydrate and free alkalis thereof. The method comprises the steps: (1) subjecting an intermediate, which is obtained through subjecting a compound with a structure represented by a formula IV shown in the description to a reaction, to a reaction with trifluoroacetate or a compound with a structure represented by a formula V or a formula VI shown in the description, and then, carrying out acid treatment, so as to obtain a compound with a structure represented by a formula I shown in the description; (2) subjecting the compound with the structure represented by the formula I to a nitration reaction under the catalysis of an acid, so as to obtain a compound with a structure represented by a formula II shown in the description; and (3) subjecting the compound with the structure represented by the formula II to nitro-to-amino reduction, thereby obtaining a compound with a structure represented by a formula III shown in the description.

QUINAZOLINONE T-TYPE CALCIUM CHANNEL ANTAGONISTS

The present invention is directed to quinazolinone compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.